Biology Department Western Wyoming Community College PHYSIOLOGY OF CARDIAC HYPERTROPHY IN SEVERELY IRON DEFICIENT RATS USING PRESSURE- VOLUME LOOPS BY: JACQUIE ZADRA, EMILY THOMPSON, AND ASHLEY WEIGEL FACULTY MENTOR: BUD CHEW, PH.D.

Enlargement of the heart  Can either be adaptive or pathological  Adaptive hypertrophy is seen in aerobic athletes  Pathological hypertrophy is seen in diseases of the heart such as congestive heart failure CARDIAC HYPERTROPHY

 Adaptive hypertrophy  Increased cardiac output  Increased heart chamber size  Healthy heart wall muscle  Pathological Hypertrophy  Decreased cardiac output  No increase in heart chamber size  Fibrotic heart wall  Due to increase in collagen ADAPTIVE VS PATHOLOGICAL HYPERTROPHY

PROLONGED IRON DEFICIENCY CAUSES CARDIAC HYPERTROPHY

 12 weeks of iron deficiency  Morphological indications of failure  Apoptosis stimulated  Cardiac function of this hypertrophy is poorly understood CURRENT UNDERSTANDING OF CARDIAC HYPERTROPHY FROM IRON DEFICIENCY Ref: Dong et al., 2007.

We hypothesized that four weeks of iron deficiency would result in failing cardiac function and decreased sympathetic neurotransmitter stores. HYPOTHESIS

 Two groups Sprague-Dawley Rats  Four rats fed iron deficient diet (AIN-93G without iron)  Four rats fed control diet (AIN- 93G)  Four weeks of the respective dietary intervention  Cardiac pressure-volume loop protocol  Plasma and hearts frozen for HPLC analysis EXPERIMENTAL DESIGN

 2 femoral vein catheters for drug infusion  1 jugular vein catheter for saline calibration  1 carotid artery exposure for PV loop transducer  Inserted into the carotid artery and passed into the left ventricle PV LOOP PROTOCOL: SURGERY

 Aortic pressure measurements and baseline cardiac function data  Inferior Vena Cava occlusion for measure of contractility  Saline calibration for parallel conductance subtraction  Dopamine infusion  Atenolol infusion  Second baseline data  Heparinized rat to prevent blood clotting  Cuvette calibration for measure of true blood volume  Collect microhematocrit samples  Centrifuge remaining blood for plasma  Freeze plasma and hearts for HPLC analysis PV-LOOP PROTOCOL: DATA COLLECTION

RESULTS: IRON DEFICIENCY Group Hematocrit (Percent) *p<0.05 Hematocrit Group Mass (grams) *p<0.05 Body Mass

RESULTS: CARDIAC HYPERTROPHY gmgm -1 Group HeartBody Mass -1 Ratio *p<0.05 Iron Deficient Control

PRESSURE-VOLUME LOOPS Stroke Volume Ejection Isovolumic Relaxation End Diastolic Volume Filling Isovolumic Contraction End Systolic PV relationship (ESPVR) Cardiac output= (SV)(HR) Heart Rate

RESULTS: PRESSURE-VOLUME LOOPS Iron Deficient-FailingIron Deficient-AdaptiveControl

CO=HR*SV RESULTS: PRESSURE-VOLUME LOOPS uLmin -1 Group *p<0.05 Cardiac Output

RESULTS: PRESSURE VOLUME LOOPS Group Heart Rate bpm Group *p<0.05 Stroke Volume uL

 Stroke volume is affected by three factors: (1) Preload  End diastolic volume RESULTS: PRESSURE VOLUME LOOPS Group *p<0.05 End Diastolic Volume uL

RESULTS: PRESSURE-VOLUME LOOPS (2) Contractility  Sympathetic nervous system  Ejection fraction  Frank-Starling Law of The Heart Group Percent *p<0.05 Ejection Fraction

 Control rat ejection fraction averaged 55%  Iron deficient rat ejection fraction averaged 93% ESPVR AS A MEASURE OF CONTRACTILITY

RESULTS: PRESSURE-VOLUME LOOPS Group mmHgs -1 dpdt -1 Max

(3) Afterload  Aortic diastolic pressure RESULTS: PRESSURE-VOLUME LOOPS Group Pressure (mmHg) Aortic Diastolic Pressure

PROLONGED IRON DEFICIENCY CAUSES CARDIAC HYPERTROPHY

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY  HPLC is a technique used to separate and quantify chemical compounds in a liquid medium  Used to determine concentration of norepinephrine in extracted plasma

RESULTS: HPLC Group NE (ugml -1 ) Plasma Norepinephrine Concentration

CONCLUSION: 3 ADAPTIVE ID HEARTS, 1 FAILING ID HEART

Thanks to Wyoming INBRE for funding our research ACKNOWLEDGMENTS